The peptides of the present invention have been shown to inhibit angiogenesis, the fundamental process by which new blood vessels are formed that is essential to a variety of normal body activities (such as reproduction, development, and wound repair). Although angiogenesis is a highly regulated process under normal conditions, many diseases (characterized as “angiogenic diseases”) are driven by persistent unregulated angiogenesis. Otherwise stated, unregulated angiogenesis may either cause a particular disease directly or exacerbate an existing pathological condition.
In many instances, the therapeutic effectiveness of a pharmaceutically active peptide depends on its continued presence in vivo over prolonged time periods. A sustained release formulation or sustained drug delivery is desirable to avoid the need for repeated administrations. Formulations which provide sustained release have been the subject of intensive research (see, for example, WO0135929; WO0074650; WO9207555; EP0949905; and U.S. Pat. Nos. 5,990,194; 6,143,314; 5,780,044; 5,945,115; 6,261,583; 6,130,200; and 5,783,205). Different approaches are often taken when formulating pharmaceutically active peptides. For example, Lupron® and Eligard®, which both contain the peptide leuprolide acetate, use different formulations for drug delivery.
Peptides useful in the treatment of conditions caused or exacerbated by angiogenesis are known (see, for example, WO99/61476). We have discovered that the sustained release properties of the aforementioned prior art formulations cannot be predictably applied to these antiangiogenic compounds. The irregularity exhibited when the known formulations are applied to pharmaceutically active peptides poses an impediment in the development of reliable sustained release formulations. Therefore, additional sustained delivery formulations for administering pharmaceutically active antiangiogenic drugs, particularly peptides, are still needed.